Synthesis of carboxylic acids by hydrolysis or deprotection
(R)-β-Hydroxy nitriles were obtained via a reduction catalyzed by a recombinant carbonyl reductase with excellent optical purity and were further converted to (R)-β-hydroxy carboxylic acids via a nitrilase-catalyzed hydrolysis. The present study allows ready access to both chiral β-hydroxy nitriles and β-hydroxy carboxylic acids of pharmaceutical importance.
D. Zhu, H. Ankati, C. Mukherjee, Y. Yang, E. R. Biehl, L. Hua, Org. Lett., 2007, 9, 2561-2563.
Simple, mild, and environmentally friendly procedures for the direct conversion of dithioesters into either carboxylic acids or esters using hydrogen peroxide under alkaline conditions are described.
F. Grellepois, C. Portella, Synthesis, 2008, 3443-3446.
The reaction of aldehydes with trichloromethide followed by reductive ring opening under basic conditions affords homologated carboxylic acids in high yields. This operationally simple procedure provides a practical, efficient alternative to other homologation protocols and is compatible with sensitive aldehydes including enals and enolizable substrates.
L. R. Cafiero, T. S. Snowden, Org. Lett., 2008, 10, 3853-3856.
The reaction of alkenyl trichloromethyl carbinols with various nucleophiles under protic basic conditions reveals that mercaptans participate by α-substitution (SN2), wheareas hydroxide prefers γ-substitution with stereoselective allylic transposition (SN2'). Regioselectivity with alkoxides depends upon alkene substitution.
J. L. Shamshina, T. S. Snowden, Org. Lett., 2006, 8, 5881-5884.
A one-carbon homologation of an alcohol to the extended carboxylic acid, ester, or amide involves a Mitsunobu reaction with an alkoxymalononitrile, followed by unmasking in the presence of a suitable nucleophile. The homologation and unmasking can even be performed in a one-pot process in high yield.
N. Kagawa, A. E. Nibbs, V. H. Rawal, Org. Lett., 2016, 18, 2363-2366.